“Observe due measure, for right timing is in all things the most important factor.”—Hesiod, Works and Days (c. 700 BC) (1)

Calcific degenerative aortic stenosis (AS) is a common cause of acquired valvular heart disease affecting predominantly older adults. Over time, accumulation of valve calcification restricts leaflet motion, leading to progressive outflow obstruction, afterload mismatch, and symptoms. Traditionally, the asymptomatic phase of severe AS (stage C) has been associated with a low risk of sudden death (2–4), such that close observation for the development of symptoms is recommended before proceeding with aortic valve replacement (AVR) (5).

In this issue of the Journal, Taniguchi et al. (6) report 5-year outcomes of the CURRENT AS (Contemporary Outcomes after Surgery and Medical Treatment in Patients with Severe Aortic Stenosis) registry of 1,808 patients with asymptomatic severe AS who were initially treated either conservatively (n = 1,517) or with initial AVR (n = 291). The authors found a higher rate of mortality (26.4% vs. 15.4%; p = 0.009) and hospitalizations for heart failure (19.9% vs. 3.8%; p < 0.001) at 5 years of follow-up in patients who were managed conservatively compared with those undergoing initial AVR. These data seemingly conflict with recommendations of watchful waiting for the development of symptoms, and beg the question, “What are we waiting for?” in the patient with asymptomatic severe AS.

One of the unique strengths of the dataset presented by Taniguchi et al. (6) is the large number of patients with severe AS who were initially managed conservatively. Most contemporary cohorts have a higher referral rate for AVR, leaving small numbers of conservatively managed patients and limiting statistical comparisons. Additionally, the authors should be commended for including hospitalizations for heart failure as part of the primary endpoint, because the development of congestive heart failure in AS represents a more advanced stage of disease that should be avoided. Interestingly, AVR mortality was higher in patients who underwent intervention after symptom onset compared with asymptomatic patients, further supporting the notion that earlier surgery may be beneficial. During a median follow-up of 2 years, 41% of patients initially managed conservatively required AVR, which is in keeping with previous estimates that progression to required intervention within 5 years of developing severe AS is almost inevitable.

Why might asymptomatic AS be a different problem now than was observed only 10 to 20 years ago? Several potential reasons for this may exist. The rate of sudden death in this study was slightly higher than previously reported (1.5% per year compared with earlier estimates of 1.0% per year) (2,3). Today, AS patients are an elderly population, often with multiple comorbidities, potentially leaving them more vulnerable to the hemodynamic derangements associated with severe AS. Furthermore, AVR mortality is lower now than it used to be and can be accurately estimated using the Society for Thoracic Surgeons risk calculator (7).

Although the study methods were robust (6), asymptomatic status was not confirmed by treadmill exercise test, therefore leaving the possibility of undetected or unrecognized symptoms in some patients due to sedentary lifestyle. In fact, the updated American College of Cardiology/American Heart Association guidelines provide a class IIa recommendation for AVR in asymptomatic patients with severe AS (stage C1) who have decreased exercise tolerance on treadmill testing (5). Furthermore, as the authors point out, monitoring for symptoms can be an imprecise undertaking and some patients will inevitably be lost to follow-up using this strategy. Although a retrospective study, the authors appropriately used a propensity score-matched cohort to minimize selection bias in comparing outcomes in patients managed conservatively versus with initial AVR. Despite these measures, the population in this Japanese-based study may have unique features compared with Western populations that limit the generalizability of the study results. The high prevalence of obesity in the United States, even in patients with severe AS (8), for instance, is not represented in this Japanese cohort with mean body mass index of 22 kg/m2, which potentially could affect AVR outcomes.

Appropriate timing of the intervention for each individual patient is essential to balance the natural risk of severe AS with the risk of AVR. This study sheds new light on optimal management strategies in asymptomatic severe AS and raises many more important questions. Ultimately, however, we await a randomized controlled trial of patients with asymptomatic severe AS to address the question of whether early AVR is preferable to a strategy in which AVR is deferred until symptoms develop.

Footnotes

↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.

Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.

(2014) 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol63:e57–e185.

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